Aged mice exhibit faster acquisition of intravenous opioid self-administration with variable effects on intake

The goal of this study was to address a critical gap in the literature regarding age-dependent effects in opioid (remifentanil and fentanyl) self-administration. Male and female C57Bl/6J and C57Bl/6NJ mice were divided into young (mean: 19 weeks) and old (mean: 101 weeks) groups and were trained to self-administer intravenous fentanyl or remifentanil in daily operant sessions. Acquisition, intake, and cue-responding after forced abstinence were measured for both drugs, and a dose-response curve and dose-escalation were conducted for remifentanil and fentanyl, respectively. Surprisingly, old mice learned to self-administer both remifentanil and fentanyl faster and more accurately than young mice. Baseline intake of remifentanil was also greater in old mice compared to the young group; however, we did not see increased intake of fentanyl with age at either dose tested. Furthermore, old mice showed greater responding for cues previously associated with remifentanil after a forced abstinence, but this result is not observed with fentanyl.